CN105237592A - Preparation method of allose derivative - Google Patents
Preparation method of allose derivative Download PDFInfo
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- CN105237592A CN105237592A CN201510599285.XA CN201510599285A CN105237592A CN 105237592 A CN105237592 A CN 105237592A CN 201510599285 A CN201510599285 A CN 201510599285A CN 105237592 A CN105237592 A CN 105237592A
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Abstract
The invention relates to a preparation method of an allose derivative. The method comprises the following steps: reacting water, chromium trioxide and pyridine at a certain temperature, cooling, filtering, and drying to obtain an oxidant pyridinium dichromate (PDC); making a reaction system by using dichloromethane, methane, the oxidant PDC and acetic anhydride, adding a diisopropylidene-alpha-D-glucofuranose solution to the system at room temperature, heating for refluxing, carrying out reduced pressure concentration, extracting the concentrate by ethyl acetate, filtering and eluting the obtained extract liquid by a column, mixing obtained eluate, and carrying out reduced pressure concentration to obtain an oxide; adding a sodium borohydride solution to the oxide in a dropwise manner at a certain temperature, reacting, extracting the obtained reaction solution with dichloromethane after the reaction is finished, drying the obtained organic layer with anhydrous magnesium sulfate, filtering and concentrating the obtained concentrate filtrate, re-crystallizing the obtained solid with ether to obtain purified diisopropylidene-alpha-D-glucofuranose.
Description
(1) technical field:
The present invention relates to organic synthesis medicine intermediate field, particularly a kind of preparation method of allose derivative.
(2) background technology:
Utilize oxidation-reduction reaction can change the configuration of hydroxyl on carbon in saccharide compound, but oxidation-reduction reaction is one of difficult point in such building-up reactions, mainly because implement oxidizing reaction to have suitable difficulty, as selected certain active oxygenant, solvent used needs drying, operation is also comparatively complicated.The oxygenant that the monose of band protecting group is oxidized to ketose is often mainly contained three major types by people, and namely dimethyl sulfoxide (DMSO) is serial, four rubidium oxides series, chromium trioxide are serial.The agent of chromium trioxide series of oxidation is cheap because of it, receives extensive concern.
BurtonCollins takes the lead in being used for by chromium trioxide-pyridine in the oxidizing reaction with protecting group sugar; obtain corresponding ketose; yield relatively low (yield is less than 50%); and the position of the oxidation of chromium trioxide-pyridine often with hydroxyl in sugar is different; reaction result differs greatly; it in sugar after protection, furan nucleus is in isolated secondary hydroxyl groups inner mold position or pyranoid ring being in equatorial bond; substantially be not oxidized or productive rate extremely low; as pitched base-α-D-glucofuranose with chromium trioxide-pyridine oxidation diisopropyl, productive rate is only 0.6%.Proposition chromium trioxide-pyridine-aceticanhydride-the dichloromethane system such as Garegg carry out oxidizing reaction in room temperature, and not only time shorten used, and oxidisability not affected by the space factor of hydroxyl.Two compounds that the discoveries such as Corey are relevant with chromium trioxide: pyridinium chloro-chromate (PCC-C
5h
5n
+hCrO
3cl
-) and pyridinium dichromate (PDC-(C
5h
5n
+h) 2Cr
2o
7 -), primary alconol and secondary alcohol can be oxidized to corresponding aldehyde and ketone with good selectivity by PCC and PDC, productive rate quite high (80% ~ 100%).Subsequently, pyridinium chloro-chromate and pyridinium dichromate are used for the synthesis of ketose by Hollenberg and Herscovici etc., and productive rate is greatly improved.The employing such as Czernecki pyridinium dichromate-acetic acid-
molecular sieve oxosugar compound yield utilizes pyridinium dichromate-aceticanhydride-dichloromethane system oxosugar diisopropyl fork base-α-D-glucofuranose also to obtain the product of close yield up to 96%, Andersson etc.
Change in the configuration reaction of hydroxyl on C in saccharide compound at above-mentioned chemical synthesis process, or be because the oxidation activity of oxygenant is more weak, and gained oxidation products purity is low, by product is more, and aftertreatment is more complicated; Oxygenant is excessive larger in addition, it is thickly be deposited on container bottom that oxidizing reaction terminates rear oxidation agent, and by wherein coated for a part of oxidation products, so not only waste considerable oxygenant, and product is also difficult to be separated, thick oxygenant is difficult to filter, and need to extract product with a large amount of solvents, the quantity of solvent expended is large.Be because the purity of products therefrom is lower, but also post need be carried out be separated and just can obtain sterling, need solvent and the time of at substantial, result in combined coefficient low.We are based on such present situation, homemade PDC is adopted to be oxygenant, the purity of oxidizing reaction products therefrom is higher, direct employing post filters and just oxidation products can be separated with oxygenant, avoid and adopt other oxygenant and demand pole chromatography comes separated product and by product, and oxidation products is not purified with regard to direct-reduction, in reduction reaction, keep the suitably excessive of reductive agent, can guarantee that reaction can be carried out completely, and final product is single-point compound; Two-step reaction is merged into successive reaction, simplifies operation, decrease loss, improve synthesis yield.Adopt homemade oxygenant pyridinium dichromate (PDC) to complete expeditiously and pitch the configuration conversion of base-α-D-glucofuranose to diisopropyl fork base-α-D-allofuranose by diisopropyl.
(3) summary of the invention:
The object of the present invention is to provide a kind of method preparing allose derivative, it is for above-mentioned situation, a kind of easy and simple to handle, with low cost, efficient preparation method of invention.
Technical scheme of the present invention: a kind of preparation can effectively control the method preparing allose derivative, it is characterized in that it comprises the following steps:
(1) preparation of oxygenant pyridinium dichromate (PDC);
By water, chromium trioxide and pyridine maintain react at a certain temperature, then add acetone, by mixture cooled and filtered, organic solvent washing, drying oxygenant pyridinium dichromate (PDC).
(2) oxidation of diisopropyl fork base-α-D-glucofuranose;
Be made into reaction system with methylene dichloride, oxygenant PDC and aceticanhydride, in this system, at room temperature add the solution of diisopropyl fork base-α-D-glucofuranose, reflux.Then concentrating under reduced pressure, extracts enriched material by ethyl acetate, and extracting solution post filters wash-out, merge elutriant, concentrating under reduced pressure oxide compound, without purifying.
(3) diisopropyl pitches synthesis and the purifying of base-α-D-allofuranose;
In oxide compound, sodium borohydride solution reaction is dripped under maintaining certain temperature, use dichloromethane extraction reaction solution after completion of the reaction, then use anhydrous magnesium sulfate drying organic layer, filter and concentrated filtrate, by gained solid Diethyl ether recrystallization, obtain the sterling of diisopropyl fork base-α-D-allofuranose.
(4) accompanying drawing illustrates:
Fig. 1 is the preparation figure of allose derivative.
(5) embodiment:
Below the form by embodiment is described in further detail foregoing of the present invention again, but this should be interpreted as that the scope of the above-mentioned theme of the present invention is only confined to following embodiment, all technology realized based on foregoing of the present invention all belong to scope of the present invention.
Embodiment 1: the preparation of oxygenant pyridinium dichromate (PDC)
Take into account in churned mechanically 500ml four-hole bottle add 50ml water, 50g chromium trioxide to being equipped with temperature, holding temperature drips 40.3ml pyridine at 15 ~ 25 DEG C in reaction system.Then in reaction solution, slowly add 200ml acetone, by ice-cold for mixture rear filtration, drying oxygenant pyridinium dichromate (PDC).
Embodiment 2: the oxidation of diisopropyl fork base-α-D-glucofuranose
350ml dry methylene chloride, 40.6g pyridinium dichromate and 44.1g aceticanhydride is added to being equipped with in thermometer, prolong and churned mechanically 1000ml four-hole bottle, holding temperature drips the solution (31.2g diisopropyl fork base-α-D-glucofuranose+50ml dry methylene chloride) of diisopropyl fork base-α-D-glucofuranose at 20 ~ 25 DEG C in reaction system, after dropwising, reflux 2h.Then concentrating under reduced pressure (being no more than 65 DEG C), enriched material is extracted by 200ml × 2 ethyl acetate, extracting solution and residue post filter (100ml100-200 order silica gel, column cap 10ml anhydrous magnesium sulfate liner), use 600ml eluent ethyl acetate again, merge elutriant, be oxidation products.
Embodiment 3: the synthesis of diisopropyl fork base-α-D-allofuranose and purifying
Elutriant (being no more than 65 DEG C) in concentrating under reduced pressure example 2, is dissolved in enriched material in ethanol (80ml ethanol+60ml water).Stir lower holding temperature at 20 ~ 25 DEG C, in 0.5h, in solution, drip sodium borohydride solution (5.6g sodium borohydride+80ml water), room temperature reaction 3h.Use 200ml × 3 dichloromethane extraction reaction solution respectively, merge organic layer, wash organic layer with 100ml, then spend the night with 100g anhydrous magnesium sulfate drying organic layer.Filter, concentrated filtrate, by gained solid Diethyl ether recrystallization, obtains white crystal, is the sterling of diisopropyl fork base-α-D-allofuranose.
Claims (4)
1. a preparation method for allose derivative, is characterized in that it comprises following three steps: the preparation of (1) oxygenant pyridinium dichromate (PDC); (2) oxidation of diisopropyl fork base-α-D-glucofuranose; (3) diisopropyl pitches synthesis and the purifying of base-α-D-allofuranose.
2. the preparation method of a kind of allose derivative according to claim 1, it is characterized in that water, chromium trioxide and pyridine to maintain to react at a certain temperature, then the solid adding acetone precipitation is oxygenant pyridinium dichromate.
3. the preparation method of a kind of allose derivative according to claim 1, it is characterized in that being made into reaction system with methylene dichloride, oxygenant pyridinium dichromate and aceticanhydride, in this system, at room temperature add diisopropyl fork base-α-D-glucofuranose, heating reflux reaction can obtain oxide compound.
4. the preparation method of a kind of allose derivative according to claim 1, in oxide compound, sodium borohydride solution reaction is dripped under it is characterized in that maintaining certain temperature, by gained solid Diethyl ether recrystallization, be the diisopropyl fork base-α-D-allofuranose of purifying.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510599285.XA CN105237592A (en) | 2015-09-15 | 2015-09-15 | Preparation method of allose derivative |
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|---|---|---|---|
| CN201510599285.XA CN105237592A (en) | 2015-09-15 | 2015-09-15 | Preparation method of allose derivative |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110128327A (en) * | 2018-02-08 | 2019-08-16 | 青县科瑞希医药技术有限公司 | A kind of green production process preparing PDC |
-
2015
- 2015-09-15 CN CN201510599285.XA patent/CN105237592A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110128327A (en) * | 2018-02-08 | 2019-08-16 | 青县科瑞希医药技术有限公司 | A kind of green production process preparing PDC |
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| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20160113 |
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| WD01 | Invention patent application deemed withdrawn after publication |